scholarly journals Mitogen-initiated synthesis and secretion of T cell growth factor(s) by a T-lymphoma cell line.

1980 ◽  
Vol 152 (5) ◽  
pp. 1436-1441 ◽  
Author(s):  
S Shimizu ◽  
Y Konaka ◽  
R T Smith

Of 12 T-lymphoma cell lines investigated, one line, EL-4 azgr (Thy-1+, Lyt-1+, Lyt-2-3-,Ia-, T-200+, sIg-, and FcR-) and, to a lesser extent, the parental cell line, EL-4, produced T cell growth factor(s) (TCGF) when stimulated by the T-cell mitogen concanavalin A (Con A). Induced production of TCGF-E was detected by 6 h and maximal at 18-24 h. Purified TCGF-E from this source had an approximately 30,000 mol wt and the biological activity of TCGF produced by whole spleen cells, including: augmentation of T cell-mitogen responses, cytotoxic T lymphocyte (CTL) proliferation support dependence, augmented generation of CTL, lack of strain specificity, and failure to stimulate resting T cells. TCGF-E is neither synthesized or secreted by this lymphoma cell line unless stimulated by Con A. X-irradiation up to 7,000 rad failed to inhibit synthesis and secretion. These observations have a practical application in providing a relatively homogeneous clonal cell product for T cell culture support and for structural and functional studies of the TCGF molecule(s). They suggest also a model for examining mechanisms of triggering production and secretion of a regulatory molecule that controls T cell functions.

1982 ◽  
Vol 156 (5) ◽  
pp. 1335-1351 ◽  
Author(s):  
A Conzelmann ◽  
A Silva ◽  
M Cianfriglia ◽  
C Tougne ◽  
R P Sekaly ◽  
...  

Somatic cell fusion between cytolytically active, T cell growth factor- (TCGF) dependent murine T cell lines (CTL lines) and noncytolytic, TCGF-independent murine T lymphoma lines has yielded two types of somatic cell hybrids (5): cytolytic hybrids, growth of which is dependent on TCGF, and hybrids with very weak or undetectable cytolytic activity which grow at the same rate with or without TCGF. Here we report that the former can produce stable variants that resemble the latter type. Some of these TCGF-independent variants still have TCGF receptors. High susceptibility to the cytotoxic effects of Vicia villosa lectin, a marker distinguishing the parental CTL lines from T lymphomas, is expressed by the TCGF-dependent hybrids but not by the TCGF-independent variants. The two types of hybrids also differ in the expression of surface glycoproteins. We propose that there exists a genetic element in the CTL line that represses the TCGF-independent replication mechanism of the T lymphoma parent in the TCGF-dependent hybrids and that this genetic element is lost or switched off in the TCGF-independent variants.


Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2271-2275 ◽  
Author(s):  
RE Donahue ◽  
YC Yang ◽  
SC Clark

Abstract Because human P40 T-cell growth factor, tentatively designated interleukin-9 (IL-9), was isolated through its ability to stimulate a human IL-3-dependent leukemic cell line (M-O7E), we tested the ability of IL-9 to support the growth and differentiation of normal hematopoietic progenitor cells from peripheral blood and bone marrow. Although the M-O7E cell line was derived from a patient with megakaryoblastic leukemia, IL-9 has not proved to be a growth or maturation factor for megakaryocytes, but instead has proved to be effective in supporting the development of erythroid bursts (BFU-E) in cultures supplemented with erythropoietin. Using highly purified progenitors from peripheral blood, IL-3 showed a BFU-E plating efficiency of 46% compared with 20% for IL-9. Because of the purity of these cell preparations and the low cell density in culture, IL-9 is likely to interact directly with erythroid progenitors. Analysis of mixing experiments and of the morphology of the BFU-E in culture indicated that IL-9 interacts preferentially with a relatively early population of IL-3-responsive BFU-E. In cultures of human bone marrow or cord blood, IL-9 selectively supported erythroid colony formation, while IL-3 and granulocyte/macrophage colony-stimulating factor additionally yielded granulocyte/macrophage colonies. Therefore, IL-9 represents a new T cell-derived cytokine with the potential for selectively stimulating erythroid development in the hematopoietic system.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2392-2392
Author(s):  
Chunyan Yang ◽  
Zibo Song ◽  
Seung-Hee Jo ◽  
Balazs Csernus ◽  
Amy Chadburn ◽  
...  

Abstract Peroxisome proliferator-activated receptor gamma is a metabolic regulator involved in maintaining glucose and fatty acid homeostasis. Besides its metabolic functions, the receptor has also been implicated in tumorigenesis. Ligands of PPAR gamma have been found to induce apoptosis in a variety of tumor cell lines including lymphomas. However, apoptosis induction may not depend on the receptor since high doses of PPAR gamma agonists are required for this process. Using cells containing or lacking PPAR gamma, we reported previously that PPAR gamma attenuates apoptosis induced by growth factor withdrawal in a murine lymphocytic cell line via a receptor dependent mechanism. PPAR gamma exerts this effect by enhancing ability of cells to maintain their mitochondrial membrane potential during growth factor deprivation. In the current study, we demonstrate that PPAR gamma is expressed in human primary T lymphoma tissues and activation of PPAR gamma protects cells from serum starvation-induced apoptosis in human T lymphoma cell lines. Further, we show that the survival effect of PPAR gamma is mediated through its actions on cellular metabolic activities. In serum-deprived cells, PPAR gamma attenuates the decline in cellular ATP and suppresses accumulation of reactive oxygen species (ROS) in favor of cell survival. Moreover, PPAR gamma regulates ROS through its coordinated transcriptional control of proteins and enzymes involved in ROS production and scavenge. Introduction of PPAR gamma into a PPAR gamma-null T lymphoma cell line leads to increased cell survival. Meanwhile, knocking down the receptor in a PPAR gamma-positive lymphoma cell line reduces cell survival rate. Our studies identify cell survival promotion as a novel activity of PPAR gamma and suggest that high expression of PPAR gamma in lymphoma cells confers on them a survival advantage that renders cells resistant to growth factor and nutrient deprivation. These findings highlight the need for further investigation into the role of PPAR gamma in lymphoma and other types of cancer prior to widespread use of its agonists as anticancer therapeutics.


1981 ◽  
Vol 153 (5) ◽  
pp. 1360-1365 ◽  
Author(s):  
R Palacios ◽  
G Moller

Concanavalin A (Con-A)-induced suppressor T cells were found to respond to T cell growth factor (TCGF) by proliferation. TCGF abrogated the suppressor activity exerted by these cells on phytohemagglutinin (PHA)- and alloantigen- induced lymphocyte proliferation and on pokeweed mitogen (PWM)-driven immunoglobulin secretion. The Con-A-activated suppressor T cells absorbed the TCGF activity, preincubation of these active suppressor cells with TCGF abolished their suppressor activity and addition of increasing numbers of Con-A-activated T cells reverted the abrogator,/ effect of TCGF. Altogether, these findings suggest that Con-A-induced suppressor T cells exert their function by decreasing the available levels of TCGF. Cyclosporin-A (CYA), which is known to inhibit the expression of receptors for TCGF on T cells, also inhibited the suppressor activity as determined in both indicator systems, namely PHA- or alloantigen-induced DNA synthesis and PWM-induced immunoglobulin synthesis. CYA made Con-A-treated T cells unresponsive to TCGF and unable to absorb the growth factor, supporting the notion that CYA inhibits the expression of TCGF receptors on T cells, a mechanism by which this drug seems to abrogate Con-A-induced suppressor T cell function.


Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2271-2275 ◽  
Author(s):  
RE Donahue ◽  
YC Yang ◽  
SC Clark

Because human P40 T-cell growth factor, tentatively designated interleukin-9 (IL-9), was isolated through its ability to stimulate a human IL-3-dependent leukemic cell line (M-O7E), we tested the ability of IL-9 to support the growth and differentiation of normal hematopoietic progenitor cells from peripheral blood and bone marrow. Although the M-O7E cell line was derived from a patient with megakaryoblastic leukemia, IL-9 has not proved to be a growth or maturation factor for megakaryocytes, but instead has proved to be effective in supporting the development of erythroid bursts (BFU-E) in cultures supplemented with erythropoietin. Using highly purified progenitors from peripheral blood, IL-3 showed a BFU-E plating efficiency of 46% compared with 20% for IL-9. Because of the purity of these cell preparations and the low cell density in culture, IL-9 is likely to interact directly with erythroid progenitors. Analysis of mixing experiments and of the morphology of the BFU-E in culture indicated that IL-9 interacts preferentially with a relatively early population of IL-3-responsive BFU-E. In cultures of human bone marrow or cord blood, IL-9 selectively supported erythroid colony formation, while IL-3 and granulocyte/macrophage colony-stimulating factor additionally yielded granulocyte/macrophage colonies. Therefore, IL-9 represents a new T cell-derived cytokine with the potential for selectively stimulating erythroid development in the hematopoietic system.


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